In silico and in vitro Estimation of Structure and Biological Affinity of 1,3- Oxazoles: Fragment-to-fragment Approach

Abstract

Background: The fragment-to-fragment approach for the estimation of the biological af-finity of the pharmacophores with biologically active molecules has been proposed. It is the next step in the elaboration of molecular docking and using the quantum-chemical methods for the complex modeling of pharmacophores with biomolecule fragments. Methods: The parameter 0 was used to estimate the contribution of -electron interactions in bio-logical affinity. It is directly related to the position of the frontier levels and reflects the donor-accep-tor properties of the pharmacophores and stabilization energy of the [Pharm꞉BioM] complex. Results: By using quantum-chemical calculations, it was found that the stacking interaction of oxa-zoles with phenylalanine is 7-11 kcal/mol, while the energy of hydrogen bonding of oxazoles with the amino group of lysine is 5-9 kcal/mol. The fragment-to-fragment approach can be applied for the investigation of the dependence of biological affinity on the electronic structure of pharmacophores. Conclusion: The founded quantum-chemical regularities are confirmed with the structure-activity relationships of substituted oxazoles.